Chronic obstructive pulmonary disease: An update for the primary physician
ABSTRACTOur understanding of how to manage chronic obstructive pulmonary disease (COPD) has advanced significantly over the past decade. Physicians should instill optimism for improved symptoms and quality of life in their patients with COPD, a previously stigmatized condition.
KEY POINTS
- A new COPD classification scheme is based on severity, symptoms, and exacerbations.
- Azithromycin 250 mg daily prevents exacerbations of COPD in those at high risk.
- Long-acting muscarinic antagonists such as aclidinium and tiotropium are first-line therapy.
- Relatively new options include roflumilast, an oral phosphodiesterase inhibitor, and indacaterol, an ultra-long-acting beta agonist that is taken once daily.
- Nondrug interventions include pulmonary rehabilitation, vitamin D supplementation, noninvasive positive-pressure ventilation, and lung-volume reduction surgery.
DOES VITAMIN D SUPPLEMENTATION HAVE A ROLE IN COPD MANAGEMENT?
Vitamin D is vital for calcium and phosphate metabolism and bone health. Low vitamin D levels are associated with diminished leg strength and falls in the elderly.60 Osteoporosis, preventable with vitamin D and calcium supplementation, is linked to thoracic vertebral fracture and consequent reduced lung function.61,62
Patients with COPD are at higher risk of vitamin D deficiency, and more so if they also are obese, have advanced airflow obstruction, are depressed, or smoke.62 Therefore, there are sound reasons to look for vitamin D deficiency in patients with COPD and to treat it if the 25-hydroxyvitamin D level is less than 10 ng/ mL (Table 6).
Vitamin D may also have antimicrobial and immunomodulatory effects.63 Since COPD exacerbations are frequently caused by infection, it was hypothesized that vitamin D supplementation might reduce the rate of exacerbations.
In a study in 182 patients with moderate to very severe COPD and a history of recent exacerbations, high-dose vitamin D supplementation (100,000 IU) was given every 4 weeks for 1 year.64 There were no differences in the time to first exacerbation, in the rate of exacerbation, hospitalization, or death, or in quality of life between the placebo and intervention groups. However, subgroup analysis indicated that, in those with severe vitamin D deficiency at baseline, the exacerbation rate was reduced by more than 40%.
Comment. We recommend screening for vitamin D deficiency in patients with COPD. Supplementation is appropriate in those with low levels, but data indicate no role in those with normal levels.
WHAT ARE THE NONPHARMACOLOGIC APPROACHES TO COPD TREATMENT?
Noninvasive positive-pressure ventilation
Nocturnal noninvasive positive-pressure ventilation may be beneficial in patients with severe COPD, daytime hypercapnia, and nocturnal hypoventilation, particularly if higher inspiratory pressures are selected (Table 7).65,66
For instance, a randomized controlled trial of noninvasive positive-pressure ventilation plus long-term oxygen therapy compared with long-term oxygen therapy alone in hypercapnic COPD demonstrated a survival benefit in favor of ventilation (hazard ratio 0.6).67
In another randomized trial,68 settings that aimed to maximally reduce Paco2 (mean inspiratory positive airway pressure 29 cm H2O with a backup rate of 17.5/min) were compared with low-intensity positive airway pressure (mean inspiratory positive airway pressure 14 cm H2O, backup rate 8/min). The high inspiratory pressures increased the daily use of ventilation by 3.6 hours per day and improved exercise-related dyspnea, daytime Paco2, FEV1, vital capacity, and health-related quality of life66 without disrupting sleep quality.68
Caveats are that acclimation to the high pressures was achieved in the hospital, and the high pressures were associated with a significant increase in air leaks.66
Comments. Whether high-pressure noninvasive positive-pressure ventilation can be routinely implemented and adopted in the outpatient setting, and whether it is associated with a survival advantage remains to be determined. The advantages of noninvasive positive-pressure ventilation in the setting of hypercapnic COPD appear to augment those of pulmonary rehabilitation, with improved quality of life, gas exchange, and exercise tolerance, and a slower decline of lung function.69
Pulmonary rehabilitation
Pulmonary rehabilitation is a multidisciplinary approach to managing COPD (Table 8).
Patients participate in three to five supervised sessions per week, each lasting 3 to 4 hours, for 6 to 12 weeks. Less-frequent sessions may not be effective. For instance, in a randomized trial, exercising twice a week was not enough.70 Additionally, a program lasting longer than 12 weeks produced more sustained benefits than shorter programs.71
A key component is an exercise protocol centered on the lower extremities (walking, cycling, treadmill), with progressive exercise intensity to a target of about 60% to 80% of the maximal exercise tolerance,72 though more modest targets of about 50% can also be beneficial.73
Exercise should be tailored to the desired outcome. For instance, training of the upper arms may help with activities of daily living. In one study, unsupported (against gravity) arm training improved upper-extremity function more than supported arm training (by ergometer).74 Ventilatory muscle training is less common, as most randomized trials have not shown conclusive evidence of benefit. Current guidelines do not recommend routine inspiratory muscle training.71
Even though indices of pulmonary function do not improve after an exercise program, randomized trials have shown that pulmonary rehabilitation improves exercise capacity, dyspnea, and health-related quality of life; improves cost-effectiveness of health care utilization; and provides psychosocial benefits that often exceed those of other therapies. Although there is no significant evidence of whether pulmonary rehabilitation improves survival in patients with COPD,71 an observational study documented improvements in BODE scores as well as a reduction in respiratory mortality rates in patients undergoing pulmonary rehabilitation.75
A limitation of pulmonary rehabilitation is that endurance and psychological and cognitive function decline significantly if exercise is not maintained. However, the role of a maintenance program is uncertain, with long-term benefits considered modest.71
Lung-volume reduction surgery
Lung-volume reduction consists of surgical wedge resections of emphysematous areas of the lung (Table 9).
The National Emphysema Treatment Trial76 randomized 1,218 patients to undergo either lung-volume reduction surgery or maximal medical therapy. Surgery improved survival, quality of life, and dyspnea in patients with upper-lobe emphysema and a low exercise capacity (corresponding to < 40 watts for men or < 25 watts for women in the maximal power achieved on cycle ergometry). While conferring no survival benefit in patients with upper-lobe-predominant emphysema and high exercise capacity, this surgery is likely to improve exercise capacity and quality of life in this subset of patients.
Importantly, the procedure is associated with a lower survival rate in patients with an FEV1 lower than 20%, homogeneous emphysema, a diffusing capacity of the lung for carbon monoxide lower than 20%, non-upper-lobe emphysema, or high baseline exercise capacity.
The proposed mechanisms of improvement of lung function include placing the diaphragm in a position with better mechanical advantage, reducing overall lung volume, better size-matching between the lungs and chest cavity, and restoring elastic recoil.76,77
Ongoing trials aim to replicate the success of lung-volume reduction using nonsurgical bronchoscopic techniques with one-way valves, coils, biologic sealants, thermal ablation, and airway stents.
